The human interleukin-2 receptor (IL2R) is being studied in order to understand specific critical components of the cell immune response in both normal and neoplastic cells. The approaches used aree based on (1) identification of key transcription regulatory sequencs in the IL2R gene; (2) identification of DNA binding proteins for the promoter region; (3) biochemical analysis of the distinction between high and low affinity IL2Rs. Using IL2R cDNA and genomic constructs, we have partially mapped the areas of the IL2R gene necessary for transcriptional activity, as determined by the ability to drive expression of the bacterial chloramphenicol acetylansferase gene following transfection of human cells. In MT-2 and HUT-102 cells (both infected with HTLV-I, promoter activity appears to increase if one removes regions more han 347 bases 5' to the cap site, suggesting the possibility of a negative regulatory element. This effect is less dramatically seen in JURKAT cells. Promoter activity is lost if one removes all regions moe han 244 bases 5' to the cap site in MT-2 and HUT-102 cells or more than 266 bases 5' to the cap site in JURKAT cells. We have also identified a putative DNA binding protein in nuclear extracts. This protein has been partially purified by heparin agarose chromatography. In order to study the biochemical distinction between high and low affinity IL2Rs, we have cross-linked 125I-IL2 (Mr 15,500) to the IL2R (Mr\50-55,000). In addition to the expected band of 68-72 kD we find a second band of 85-92 kD. Immunoprecipitations with anti-IL2R antibodies only precipitate the 68-72 kD band. We believe that the upper band represents Il-2 cross-linked to a high affinity IL2R specific associated subunit, which confers high affinity binding properties to the IL2R.